Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands.
Cell Microbiol. 2009 May;11(5):825-41. doi: 10.1111/j.1462-5822.2009.01298.x. Epub 2009 Feb 10.
Bioluminescence imaging (BLI) is a powerful new method to study virus dissemination in the live animal. Here we used this method to monitor the spatial and temporal progression of mouse hepatitis coronavirus (MHV) infection in mice using luciferase-expressing viruses. Upon intranasal inoculation, virus replication could initially be observed in the nasal cavity and the cervical lymph nodes, after which the infection spread to the brain and frequently to the eyes. The kinetics of virus spread to and clearance from the brain appeared to depend on the inoculation dose. After intraperitoneal inoculation, virus replication was predominantly observed in the liver and occasionally in the intestines, but interestingly also in the tail and paws. BLI thus elucidated new anatomic locations of virus replication. Furthermore, MHV dissemination was shown to be critically depended on the viral spike protein, but also on the mouse strain used. Widespread dissemination was observed in mice lacking a functional type I interferon response. The importance of the type I interferon system in limiting viral spread was also demonstrated by the administration of type I interferons to mice. Our results provide new insights in coronavirus pathogenesis and demonstrate the potential of BLI to study coronavirus-host interactions in vivo.
生物发光成像（BLI）是一种强大的新方法，可用于研究活体动物中的病毒传播。在这里，我们使用这种方法，使用表达荧光素酶的病毒来监测小鼠肝炎冠状病毒（MHV）感染在小鼠中的空间和时间进展。通过鼻腔接种，病毒复制最初可在鼻腔和颈部淋巴结中观察到，随后感染扩散到大脑，并经常扩散到眼睛。病毒从大脑传播和清除的动力学似乎取决于接种剂量。通过腹腔接种，病毒复制主要在肝脏中观察到，偶尔在肠道中观察到，但有趣的是也在尾巴和爪子中观察到。BLI 因此阐明了病毒复制的新解剖部位。此外，MHV 的传播被证明严重依赖于病毒的刺突蛋白，但也依赖于所用的小鼠品系。在缺乏功能性 I 型干扰素反应的小鼠中观察到广泛的传播。I 型干扰素系统在限制病毒传播中的重要性也通过向小鼠施用 I 型干扰素得到证明。我们的结果提供了冠状病毒发病机制的新见解，并证明了 BLI 在体内研究冠状病毒-宿主相互作用的潜力。
